A polyelectrolyte handle for single-molecule force spectroscopy

Single-molecule force spectroscopy is a powerful tool for the quantitative investigation of the biophysics, polymer physics and mechanochemistry of individual polymer strands. One limitation of this technique is that the attachment between the tip of the atomic force microscope and the covalent or noncovalent analyte in a given pull is typically not strong enough to sustain the force at which the event of interest occurs, which makes the experiments time-consuming and inhibits throughput. Here we report a polyelectrolyte handle for single-molecule force spectroscopy that offers a combination of high (several hundred pN) attachment forces, good (similar to 4%) success in obtaining a high-force (>200 pN) attachment, a non-fouling detachment process that allows for repetition, and specific attachment locations along the polymer analyte.